Molecular Dynamic Simulation to Explore the Molecular Basis of Btk-PH Domain Interaction with Ins(1,3,4,5)P4

Table 1

Ranked calculated binding free energies (kcal/mol) using MM/PBSA for the twelve protein-ligand systems.

	ELE	VDW	PB	SA	PBTOT	𝑇Δ𝑆	Δ𝐺bind
WT	−3031.77; (9.01^a)	−0.16; (0.07)	2961.60; (7.63)	−4.28; (0.47)	−74.61; (5.10)	−45.29; (1.43)	−29.32; (1.49)
K12R-R28C	−3119.66; (10.33)	−0.12; (0.05)	3044.04; (8.61)	−4.25; (0.18)	−79.99; (3.37)	−52.50; (1.45)	−27.49; (1.06)
K19E	−3143.08; (8.92)	−0.17; (0.03)	3069.08; (7.38)	−4.21; (0.16)	−78.38; (5.33)	−51.09; (1.60)	−27.29; (0.73)
K12R-R28H	−3029.46; (8.74)	−0.05; (0.02)	2962.73; (6.43)	−4.12; (0.21)	−73.30; (2.02)	−51.66; (1.37)	−21.64; (0.66)
E41K	−2855.47; (7.73)	−0.28; (0.16)	2789.39; (5.95)	−4.16; (0.23)	−70.52; (3.12)	−50.08; (1.52)	−20.44; (0.38)
K12R	−2922.34; (9.17)	−0.08; (0.03)	2859.80; (8.38)	−4.30; (0.21)	−66.92; (3.62)	−52.84; (1.57)	−14.08; (0.94)
R28C	−2612.17; (5.95)	−1.90; (0.23)	2552.82; (5.03)	−3.69; (0.16)	−64.94; (1.87)	−57.28; (2.47)	−7.66; (0.03)
R28H	−2591.08; (6.16)	−1.61; (0.17)	2533.38; (4.65)	−3.70; (0.17)	−63.01; (1.16)	−56.80; (2.54)	−6.21; (0.02)
S14F	−2573.79; (7.06)	−3.37; (0.74)	2545.38; (6.99)	−3.42; (0.25)	−35.20; (2.47)	−57.49; (3.02)	22.29; (0.98)
L11P	−2599.24; (7.61)	−1.75; (0.41)	2578.10; (6.70)	−3.94; (0.33)	−26.83; (1.42)	−58.75; (4.47)	31.92; (2.02)
Y40N	−2550.35; (7.0)	−2.57; (0.59)	2531.48; (6.23)	−3.92; (0.27)	−25.36; (1.84)	−58.34; (3.89)	32.98; (1.68)
F25S	−2501.74; (7.17)	−2.59; (0.69)	2487.39; (6.64)	−3.77; (0.19)	−20.71; (1.54)	−58.32; (4.15)	37.61; (1.82)

aThe statistical error was estimated on the basis of the deviation between block averages.
ELE: electrostatic energy; VDW: van der Waals energy; PB: the PB solvation energy; SA: the surface area energy (nonpolar solvation energy); PBTOT: sum of ELE, VDW, PB, and SA.
The absolute temperature (𝑇) was set to 300 K in the MM-PBSA calculations. Δ𝐺_bind: subtracting 𝑇Δ𝑆 from PBTOT.